title: Quantitative proteomics identifies the Myb-binding protein p160 as a novel target of the von Hippel-Lindau tumor suppressor.
abstract: BACKGROUND
  The von Hippel-Lindau (VHL) tumor suppressor gene encodes a component of a ubiquitin ligase complex, which is best understood as a negative regulator of hypoxia inducible factor (HIF). VHL ubiquitinates and degrades the α subunits of HIF, and this is proposed to suppress tumorigenesis and tumor angiogenesis. However, several lines of evidence suggest that there are unidentified substrates or targets for VHL that play important roles in tumor suppression.
  
  
  RESULTS
  Employing quantitative proteomics, we developed an approach to systematically identify the substrates of ubiquitin ligases and using this method, we identified the Myb-binding protein p160 as a novel substrate of VHL.
  
  
  CONCLUSIONS
  A major barrier to understanding the functions of ubiquitin ligases has been the difficulty in pinpointing their ubiquitination substrates. The quantitative proteomics approach we devised for the identification of VHL substrates will be widely applicable to other ubiquitin ligases.
authors.affiliation: Greehey Children's Cancer Research Institute, San Antonio, Texas, United States of America.
authors.forename: Yanlai
authors.initials: Y
authors.lastname: Lai
authors.forename: Mei
authors.initials: M
authors.lastname: Qiao
authors.forename: Meihua
authors.initials: M
authors.lastname: Song
authors.forename: Susan T
authors.initials: ST
authors.lastname: Weintraub
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Shiio
mesh_terms: D000818:Animals; D041702:BALB 3T3 Cells; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D003676:Deferoxamine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D007976:Leupeptins / Q000494:pharmacology; D051379:Mice; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D040901:Proteomics / Q000379:methods; D016601:RNA-Binding Proteins; D017262:Siderophores / Q000494:pharmacology; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000378:metabolism / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D007976:Leupeptins; C110421:Mybbp1a protein, mouse; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D017262:Siderophores; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D046988:Proteasome Endopeptidase Complex; D003676:Deferoxamine; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde